Maturation and Mip-1β Production of Cytomegalovirus-Specific T Cell Responses in Tanzanian Children, Adolescents and Adults: Impact by HIV and Mycobacterium tuberculosis Co-Infections

PLoS One. 2015 May 14;10(5):e0126716. doi: 10.1371/journal.pone.0126716. eCollection 2015.

Abstract

It is well accepted that aging and HIV infection are associated with quantitative and functional changes of CMV-specific T cell responses. We studied here the expression of Mip-1β and the T cell maturation marker CD27 within CMVpp65-specific CD4(+) and CD8(+) T cells in relation to age, HIV and active Tuberculosis (TB) co-infection in a cohort of Tanzanian volunteers (≤ 16 years of age, n = 108 and ≥ 18 years, n = 79). Independent of HIV co-infection, IFNγ(+) CMVpp65-specific CD4(+) T cell frequencies increased with age. In adults, HIV co-infection further increased the frequencies of these cells. A high capacity for Mip-1β production together with a CD27(low) phenotype was characteristic for these cells in children and adults. Interestingly, in addition to HIV co-infection active TB disease was linked to further down regulation of CD27 and increased capacity of Mip-1β production in CMVpp65-specific CD4+ T cells. These phenotypic and functional changes of CMVpp65-specific CD4 T cells observed during HIV infection and active TB could be associated with increased CMV reactivation rates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age Factors
  • CD4-Positive T-Lymphocytes / immunology*
  • CD4-Positive T-Lymphocytes / virology
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / virology
  • Chemokine CCL4 / metabolism*
  • Child
  • Cohort Studies
  • Coinfection / immunology
  • Cytomegalovirus / immunology
  • Cytomegalovirus Infections / complications
  • Cytomegalovirus Infections / immunology*
  • Cytomegalovirus Infections / virology
  • HIV Infections / complications
  • HIV Infections / diagnosis
  • HIV Infections / immunology*
  • Humans
  • Interferon-gamma / metabolism
  • Male
  • Phosphoproteins / metabolism
  • Risk Factors
  • Tanzania
  • Tuberculosis / complications
  • Tuberculosis / diagnosis
  • Tuberculosis / immunology*
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Viral Matrix Proteins / metabolism
  • Young Adult

Substances

  • Chemokine CCL4
  • Phosphoproteins
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Matrix Proteins
  • cytomegalovirus matrix protein 65kDa
  • Interferon-gamma

Grants and funding

The authors gratefully acknowledge funding from the European and Developing Countries Clinical Trials Partnership (EDCTP) for this study as part of the TB CHILD project (IP.2009.32040.007). Co-funding was provided by the German Federal Ministry of Education and Research (BMBF Grant 01KA1006), the Swiss National Science Foundation (32EC30_131192/1) and the German Research Foundation (DFG, grant SA 1878/1-1). Christof Geldmacher`s salary is funded by the German Center for Infection Research (DZIF). Damien Portevin’s salary was funded by the Basel University (Förderung exzellenter junger Forschender). Philipp Metzger was supported by the German Academic Exchange Service (DAAD) with a PROMOS scholarship.